Introduction

Ulcerative proctitis (UP) is an uncommon presentation in paediatric patients with ulcerative colitis, accounting for <10% of cases in most studies. Therefore, there is limited data on the clinical features and outcomes of these paediatric patients.

Aims & Methods

We aimed to characterize the clinical features and natural history of UP in children, and identify predictors of poor outcomes in a retrospective cohort study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged<18 years diagnosed with UP between 01/01/2016-31/12/2020. Associations between baseline characteristics at diagnosis of UP and different clinical outcomes were evaluated using univariable and multivariable Cox regression.

Results

Data were collected from 196 patients (median age at diagnosis 14.5 [IQR 11.9-15.9] years, 105 females [53.6%]). The most common presenting features were bloody stools (95%), abdominal pain (60%) and diarrhea (47%). The median Pediatric Ulcerative Colitis Activity Index (PUCAI) score at the time of diagnosis was 25 (IQR 20-35), with only 2 patients (1.1%) presenting with acute severe colitis (ASC). 125 patients (67.9%) had a PUCAI score of <35, reflecting mild clinical disease activity. Nevertheless, the majority of patients exhibited moderate-severe endoscopic inflammation, with a Mayo score of 2 in 103 (54.2%) and 3 in 40 (21.1%) patients. Most patients had normal inflammatory markers and albumin levels and the median fecal calprotectin value was 645 (IQR 238-1435) mcg/g, with 13/132 (9.8%) and 28/132 (21.2%) having a level of <100 mcg/g or <250 mcg/g, respectively. By the end-of-induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 52%, 50% 73%, respectively.
The median time to last follow-up was 2.7 (IQR 1.7-3.8) years. The rates of treatment escalation to oral steroids, thiopurines and biologics at 1, 3 and 5 years were 17.6%, 32.6% and 57.8%, 9.8 %, 24.3% and 43.2%, and 10.4%, 22.0% and 42.8%, respectively. Subsequent episodes of ASC were uncommon, involving up to 20% of the patients within 5 years of diagnosis. Nevertheless, IBD-related admissions were frequent, reaching 11.3%, 23.2% and 33.7% within 1, 3 and 5 years from diagnosis, respectively. Finally, only 6 patients (3.1%) had a colectomy by the end of follow-up. On multivariable cox regression analysis, only the PUCAI score was associated with poor outcomes, with a score ≥35 providing increased risk, including escalation to biologics (HR 3.5 [95% CI 1.8-6.6, P<0.001]), subsequent ASC event [HR 2.7 (95% CI 1.3-5.7, P=0.009]) and IBD-associated admission (HR 2.3 [95% CI 1.2-4.2, P=0.008]).
48% of patients that presented with UP and were rescoped exhibited proximal disease progression during follow-up. The presence of cecal patch at the diagnostic colonoscopy was more frequent in patients that subsequently exhibited proximal disease progression (4/58 [6.9%]) vs 11/51 [ 21.6%], [P=0.027).Moreover, the PUCAI score at the end-of-induction was significantly higher in patients that had subsequent disease progression.

Conclusion

This is the largest cohort, to date, of paediatric patients with UP. Children with UP exhibit high rates of proximal disease extension and requirement of systemic immunosuppressive medications, in the first years after diagnosis. Providers should consider to apply treat-to-target approaches, similar to other patients with UC, in the care of these patients with repeated sigmoidoscopies to document mucosal healing and a specific focus on quality-of-life measurements.

Disclosure

DES received payment or honoraria for contracts from Abbvie, lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Dr. Reddy’s, Montavit, Noventure, Nutricia, and Reckitt Benckiser, support for attending meetings from Nestle, not related to this study; KLK received consulting fees from Abbvie, Biocodex and Tillots pharma and a grant from Pediatric Research Foundation (Finland) and aa grant from Helsinki University Hospital Research Fund; DSS received consulting fees from AbbVie and a research grant from Takeda.

Introduction

Immunomodulators and biologicals play an essential role in current IBD management, but are associated with increased risk of infections. In light of the growing number of treatment options, the benefit-risk balance of drugs is becoming increasingly important in clinical decision making. Post-marketing surveillance studies are pivotal to assess infection risk, yet mainly focus on severe infections. As a result, data on mild and moderate infections are scarce. However, mild and moderate infections take longer to clear in immunosuppressed patients, have been reported to be the most burdensome adverse drug reaction according to patients, and can negatively influence drug adherence.

Aims & Methods

Aim: To assess the incidence of all infections and identify risk factors for the development of infections in IBD patients.
Methods: We previously developed and validated a Patient-Reported Infections Questionnaire (PRIQ), with excellent diagnostic accuracy, covering 15 infection categories with a 3-month recall period. [1] The current prospective, multicentre, observational cohort study was performed between Jun, 1 2020 and Jul, 1 2021, enrolling consecutive IBD patients and using the PRIQ which was implemented in myIBDcoach, an established telemedicine platform. Infection severity was defined as mild (self-limiting or topical treatment), moderate (oral antibiotics, antivirals or antifungals) or severe (hospitalization or IV treatment). Incidence rates (IR) were calculated for all infections, stratified for severity and subtype. Multivariable logistic regression, adjusting for relevant confounders, was performed to identify risk factors for infections.

Results

In total, 629 IBD patients (n=346 CD, n=283 UC, 58.3% female, mean age at cohort entry 48.3 years [SD 14.8], mean disease duration 12.4 years [SD 10.8]) were included which completed 2391 PRIQs during 572 person-years (PY) of follow-up. This resulted in 990 reported infections, corresponding to IRs of 17.3, 11.8, 5.1, and 0.4 per 10PY for all, mild, moderate, and severe infections, respectively. Upper respiratory tract (IR 26.9/100PY) and urinary tract infections (IR 14.8/100PY) were the most commonly reported mild and moderate infections types, respectively (Table 1). Compared to patients without treatment, patients on immunosuppressive treatment more frequently experienced infections of any severity (mild vs. no treatment: IR ratio (IRR) 1.57 [95%CI 1.21-2.06] p<0.001, moderate vs. no treatment: IRR 1.42 [95%CI 1.20-1.69] p<0.001). On multivariable logistic regression, female sex (mild adjusted odds ratio [aOR] 1.96 [95%CI 1.38-2.79]; moderate aOR 1.71 [95%CI 1.15-2.54]), smoking status (mild aOR 1.66 [95%CI 1.15-2.41]; moderate aOR 1.86 [95%CI 1.05-3.28]), higher BMI (moderate aOR 1.05 [95%CI 1.02-2.00]), and more comorbidities (mild aOR 2.41 [95%CI 1.46-3.98]; moderate aOR 1.82 [95%CI 1.07-3.11]) were all significantly associated with the development of mild and moderate infections.

Conclusion

​In this real-world prospective study, immune suppressive therapy was associated with mild and moderate infections of any kind in IBD patients. These infections particularly occur in females, smokers, patients with higher BMI and more comorbidities. This information should be considered in personalised treatment selection.

References

[1] Rezazadeh Ardabili A, van Esser D, Wintjens D, et al. Development and validation of a remote monitoring tool for assessment of mild, moderate, and severe infections in Inflammatory Bowel Disease [published online ahead of print, 2023 Feb 16]. J Crohns Colitis. 2023;jjad023. doi:10.1093/ecco-jcc/jjad023

Disclosure

M.P. reports grants and non-financial support from Falk Pharma, grants from European commission, grants from ZonMw (Dutch national research fund), grants and non-financial support from Takeda, grants and non-financial support from Johnson and Johnson, grants and non-financial support from Abbvie, non-financial support from Ferring, non-financial support from Immunodiagnostics, non-financial support from MSD, all outside the submitted work. D.J. reports grants from Top Knowledge Institute (Well on Wheat), grants from Horizon 2020 DISCOvERIE, grants from NWO-CCC Partnership program (Carbokinetics), all outside the submitted work. Z.M. reports grants form MLDS, Niels Stensen Fellowship and Galapagos. A.v.B. has served as speaker, adviser and/or principal investigator for AbbVie, Arandal, Arena, Celgene, Ferring, Galapagos, Janssen, MSD, Pfizer, Roche, Takeda, TEVA, and received research grants from Pfizer, TEVA, Eurostars funding, ZonMw, all outside the submitted work.
The other authors have nothing to disclose relevant to this publication.

Introduction

Nowadays, Non-Alcoholic Fatty Liver Disease (NAFLD) is a leading cause of liver disease and liver transplantation. Although obesity is a well-recognized risk factor for NAFLD, there are data to support that not all patients with NAFLD are necessarily obese. However, the evidence on the prevalence and risk factors for NAFLD in lean individuals with Inflammatory Bowel Disease (IBD) is scarce.

Aims & Methods

The aim of the study was to assess the prevalence and risk factors for NAFLD in lean population with IBD. This is a cross-sectional, case control study including lean individuals with IBD (cases) and lean individuals without IBD (controls), matched for age and sex. Patients with risky alcohol consumption, previous diagnosis of chronic liver disease (immune, viral, genetic) and secondary causes of NAFLD were excluded. All included patients were performed a liver ultrasound, transient elastography and laboratory tests. Lean individuals were defined as Body Mass Index < 25 kg/m², and NAFLD as ultrasound steatosis and/or Controlled Attenuation Paremeter >248 dB/m. A descriptive analysis was carried out, and the relationship between variables was assessed using Chi square test/Fisher´s test (categorical variables) or T-student/Mann-Whitney U test (quantitative variables), as appropiate. In addition, a multivariate analysis was performed, presented as adjusted Odds Ratio (OR) and 95% Confidence Interval (95%CI).

Results

A total of 443 participants, 363 lean cases and 80 lean controls, were included in the study. No differences were observed in terms of age, sex and metabolic risk factors between both groups (Table 1). The prevalence of NAFLD in lean individuals with IBD was significantly higher compared to lean individuals without NAFLD (22% vs. 10%, p=0.015). Multivariate analysis confirmed that IBD was an independent risk factor for NAFLD in lean population (OR 2.75 95%CI (1.18-6.41)). In addition, male sex (OR 1.78 95%CI (1.04-3.05)) and older age (OR 1.03 95%CI (1.01-1.05)) were identified as risk factors for NAFLD in lean individuals.

Table 1. Baseline characteristics of cases and controls.

Conclusion

The prevalence of NAFLD is significantly higher in lean population with IBD, suggesting that IBD could play a role in the development of NAFLD in lean individuals.

Disclosure

This project has received funding from “Diputación General de Aragón” (code: DGACOVID-02).

Introduction

Inflammatory bowel diseases (IBD) are a distinct class of gastrointestinal disorders mainly represented by Crohn’s Disease (CD) and Ulcerative Colitis (UC). The dysregulation of microRNAs (miRNAs), a class of conserved endogenous, small non-coding RNA molecules, both tissue-derived and circulating, have shown to be promising biomarkers in IBD. These biomarkers can be useful for differential diagnosis, drug response prediction and can have prognostic value for the evolution of the disease. Moreover, miRNAs are interesting tools for potential future therapeutic approaches by miRNA antagonists or mimics [1].

Aims & Methods

In this study we aimed to perform a preliminary screening of a large panel of 179 miRNAs in the plasma of 6 patients with IBD and 12 non-IBD patients (CTRL) in order to identify a set of highly dysregulated miRNAs to be investigated in a larger cohort. Isolation of miRNAs has been conducted using miRNeasy Serum/Plasma Kit and the miRNAs expression has been evaluated using the Human serum/plasma focus, MIRCURY LNA miRNA Focus PCR panel (Qiagen) by qRT-PCR. After excluding 29 miRNAs that were not expressed in the investigated samples, we identified miR-19a-3p and miR-17-5p as the most stable miRNAs by the RefFinder analysis. Thus, the Ct values of the other 148 miRNAs have been normalized against the geometric mean of these two miRNAs as endogenous controls using the 2^-DCt method. All the clinical, sociodemographic and miRNAs expression data have been analyzed using SPSS. Categorical variables were tested by means of the chi-square test, and continuous variables with t-test or the non-parametric Man Whitney test, according to the normality of the data distribution.

Results

The two groups were age matched (mean age IBD= 45.83±21.27, mean age CTRL = 50.08±8.16, p=0.543) and did not differ for sex distribution (IBD= 33.3% female, CTRL=58.3% female, χ2= 1.00 and p=0.317). The statistical analysis revealed 45 miRNAs differentially expressed (p<0.05). In particular, we identified 29 overexpressed miRNAs (miR-223-3p, miR-143-3p, let-7f-5p, miR-30b-5p, miR-26a-5p, let-7a-5p, miR-142-3p, miR-374a-5p, miR-339-5p, miR-150-5p, miR-454-3p, let-7d-5p, miR-29a-3p, miR-146a-5p, miR-199a-3p, miR-221-3p, miR-142-5p, miR-191-5p, miR-338-3p, let-7g-5p, miR-103a-3p, miR-23a-3p, miR-145-5p, miR-374b-5p, miR-24-3p, miR-107, miR-27b-3p, let-7c-5p, miR-26b-5p) in the IBD group compared with the CTRL showing a fold regulation (FR)>1.5 and 7 miRNAs underexpressed reporting a FR<-1.5 (miR-421, miR-320d, miR-106b-3p, miR-320c, miR-20b-5p, miR-320b, miR-486-5p).
Notably, the expression of let-7a-5p that was upregulated in the IBD group (FR=2.45; p=0.001) positively correlated with the years of disease duration (p=0.01, Pearson r=0.919). The same positive correlation was observed for miR-30b-5p (p=0.049, Pearson r=0.812).

Conclusion

The reported data, showing 45 miRNAs differentially expressed in the plasma of IBD patients compared to controls, represent preliminary results that must be validated. The most statistically significant dysregulated miRNAs, as well as those that correlated with the years of disease duration and other clinical parameters will be investigated in a large IBD cohort in order to examine the potential value of these miRNAs as diagnostic and prognostic biomarkers.
This investigation received financial support from ICGEB (Contract No. CRP/22/019, ICGEB Ref. No. CRP/ROU21-01)

References

1. James JP, Riis LB, Malham M, Høgdall E, Langholz E, Nielsen BS. MicroRNA Biomarkers in IBD-Differential Diagnosis and Prediction of Colitis-Associated Cancer. Int J Mol Sci. 2020 Oct 24;21(21):7893. doi: 10.3390/ijms21217893. PMID: 33114313; PMCID: PMC7660644.

Introduction

Being two immune-mediated diseases (IMIDs), the association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is plausible, but data in the literature are conflicting.

Aims & Methods

The aim of our study was to evaluate the possible association between IBD and MS in a cohort of patients with IBD.

Results

In a retrospective study, we examined the medical records of 5,739 patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2022.
Among these patients, we identified 14 with MS, with a prevalence of 0.24%. The reported prevalence of MS in general population in northern Italy in 2021 was 0.18% (P = 0.24). For each of the patients with MS identified, more than ten patients without MS were analyzed. The 14 MS cases were then compared with 342 controls. From the 14 MS patients, 12 (85.7%) were female and 2 (14.3%) were male, while in the control group, 158 (46.2%) were female and 184 (53.8%) were male (P = 0.004). As for therapy, significant differences were found on mesalazine (5 (41.7%) cases vs. 317 (92.7%) controls, P < 0.0001) and anti-TNF treatment (0% cases vs 26.6% controls, P = 0.03, respectively) at the time of MS diagnosis. Moreover, Kaplan-Meier curve analysis showed that the 20-year survival probability was 98.4% for patients with IBD, while for patients diagnosed with MS and IBD it was 82.1% (P = 0.02).

Conclusion

In conclusion, patients with IBD have a similar risk of developing MS compared to the general population, but female sex appears to increase the risk. Indeed, life expectancy at 20 years for patients with IBD and MS is lower than for patients with IBD alone.

Introduction

As the therapeutic armamentarium for inflammatory bowel diseases (IBD) is rapidly expanding, it is of increasing importance to optimize treatment sequencing. However, head-to-head trials comparing efficacy of vedolizumab (VDZ) in bio-naïve versus bio-experienced patients are scarce.

Aims & Methods

Aim: To compare the effectiveness of VDZ in bio-naïve versus bio-experienced patients with IBD in a real world setting.
Methods: A retrospective monocentric study was performed in IBD patients treated with VDZ at a Belgian University Hospital, from January 2018 to June 2021 with follow-up until December 2021. Primary endpoints considering efficacy after induction and after 1 year of therapy were: clinical response (CRp) and remission (CRm), biochemical response (BRp) and remission (BRm) and endoscopic response (ERp) and remission (ERm). Secondary endpoint was treatment survival during follow-up. For assessment of risk factors influencing efficacy and treatment survival, a multivariate logistic regression and Cox regression model (CRM) were applied.

Results

A total of 84 patients were treated with VDZ, 42 bio-naïve and 42 bio-experienced. At baseline, significantly more bio-experienced patients had prior intestinal resection (IR) (40.5% (17/42) vs. 16.7% (7/42), P=0.016), used an immunomodulator (IMM) (35.7% (15/42) vs. 16.7% (7/42), P=0.047) and had a longer disease duration (12.5 vs. 3.5 years, P<0.001). Bio-naïve patients had more moderate to severe comorbidities (21.4% (9/42) vs. 2.4% (1/42), P=0.007). After VDZ induction, CRp rate was higher in bio-naïve patients (60.9% (39/42) vs 39.1% (25/42), P<0.001). Multiple logistic regression analyses revealed that bio-naïve patients had a higher chance reaching CRp (aOR 14.69, 95%CI [3.12-69.14], P<0.001)(table). CRm was reached in 35.7% bio-naïve and 19% bio-experienced patients (P=0.087). No significant difference in BRp (P=0.932) or BRm (P=0.730) rate was found . A significantly higher ERp rate was seen in bio-naïve patients (90.3% (28/31) vs. 66.7% (18/27), P=0.027). Multiple logistic regression analyses showed a trend towards higher ERp rate in bio-naïve patients (aOR 4.65, [0.99-21.84], P= 0.051)(table). No significant difference was seen for ERm (32.3 % (10/31) vs. 11.1% (3/27), P=0.054). After 1 year of VDZ, CRp was significantly higher in bio-naïve patients (82.9% (34/41) vs. 62.5% (25/40), P=0.039). Multiple logistic regression analyses showed no significant difference between both groups. Univariate analyses showed significantly higher CRm rate in bio-naïve patients (70.7% (29/41) vs. 37.5% (15/40), P=0.003). After adjustment for age, disease duration, IMM use and prior IR, this difference was no longer significant. Patients without prior IR had significantly higher odds of reaching CRm (aOR 4.33,[1.13-16.59], P=0.032). No significant difference was seen for BRp (P=0.443) and BRm (P=0.313), nor for ERp (P=0.184) or ERm (P=0.061) in univariate analyses. Cox regression analysis showed significantly longer treatment survival in bio-naïve patients (aHR 2.32, [1.03-5.23], P=0.043).

Conclusion

In this tertiary real-world cohort of patients treated with VDZ, overall, a better efficacy was seen in bio-naïve compared to bio-experienced patients.

Disclosure

No conflict of interest

Introduction

Interleukin 33 (IL-33) is a pro-inflammatory cytokine that has been implicated in the pathophysiology of inflammatory bowel disease (IBD), ulcerative colitis (UC) in particular. IL-33 as a cytokine and an alarmin might evoke systemic inflammation, which could have ramifications for the functioning of the central nervous system, contributing to mood and sleep disorders. Disruptions in IL-33 concentration are well known to occur in the course of numerous psychiatric disorders as well as obstructive sleep apnea, a condition characterized by chronic low-grade inflammation and sleep fragmentation. To date, however, this protein has not been studied in relation to insomnia or poor sleep quality, frequently comorbid to chronic inflammatory and psychiatric diseases.

Aims & Methods

The study aimed to compare serum IL-33 concentrations of IBD patients and healthy controls as well as evaluate the association between the expression level of this interleukin, depression, sleep quality, and insomnia. IBD patients (n=81) and healthy controls (HC=44) were recruited. Harvey-Bradshaw index or partial Mayo were applied in the assessment of clinical disease activity for Crohn’s disease (CD) or UC respectively. Venous blood samples as well as questionnaires: Beck Depression Inventory (BDI), Epworth sleepiness scale (ESS), Athens Insomnia Scale (AIS), and Pittsburgh Sleep Quality Index (PSQI) were collected. Human IL-33 High Sensitivity Magnetic Luminex Performance Assay was used for the analysis of serum IL-33 protein concentration according to the manufacturer’s protocol. Fluorescence measurements were taken with MAGPIX, Luminex. The study has been funded by National Science Centre, Poland (2018/31/N/NZ5/03715).

Results

No differences were noted regarding IL-33 concentrations, sleep, or psychological variables between IBD patients and HC, except for sleep efficiency, which was higher in HC (p=0.004). Only in the IBD group, a positive correlation between IL-33 concentration and BDI, PSQI, and AIS (R=0.521, p=0.003; R=0.458, p=0.01; R=0.40, p=0.03), as well as negative one with sleep efficiency (R=-0.475, p=0.008) was noted. IBD individuals with high scores on ESS or PSQI (ESS>10, PSQI>5) had elevated IL-33 serum level compared to IBD patients without sleep problems (IL-33 concentration [pg/ml]: 53.385 (30.070-313.020) vs 18.795 (11.790-26.175), P=0.01 for PSQI; 270.900 (156.225-438.680) vs 21.840 (11.870-47.720), P=0.006 for ESS). IL-33 concentrations and questionnaire scores were comparable in patients with different disease activity. As for IBD types, in the CD, but not the UC group, IL-33 was positively correlated with the severity of depression symptoms and poor sleep quality (R=0.581, p=0.02; R=0.531, p=0.03) and negatively with sleep efficiency (R=-0.667, p=0.005).

Conclusion

IL-33 might be associated with mood and sleep disorders in IBD. It could exert its effect by promoting systemic and neuroinflammation, thus negatively affecting the well-being of IBD patients. Further research on the subject of changes in mental health of IBD patients in the context of anti-inflammatory or immunosuppressive treatment would be valuable.